Sphingolipid Metabolism in Tumor Cells

Sphingolipids are a diverse family of complex lipids typically composed of a sphingoid base bound to a fatty acid via amide bond. The metabolism of sphingolipids has long remained out of focus of biochemical studies. Recently, it has been attracting an increasing interest of researchers because of different and often multidirectional effects demonstrated by sphingolipids with a similar chemical structure. Sphingosine, ceramides (N-acylsphingosines), and their phosphorylated derivatives (sphingosine-1-phosphate and ceramide-1-phosphates) act as signaling molecules. Ceramides induce apoptosis and regulate stability of cell membranes and cell response to stress. Ceramides and sphingoid bases slow down anabolic and accelerate catabolic reactions, thus suppressing cell proliferation. On the contrary, their phosphorylated derivatives (ceramide-1-phosphate and sphingosine-1-phosphate) stimulate cell proliferation. Involvement of sphingolipids in the regulation of apoptosis and cell proliferation makes them critically important in tumor progression. Sphingolipid metabolism enzymes and sphingolipid receptors can be potential targets for antitumor therapy. This review describes the main pathways of sphingolipid metabolism in human cells, with special emphasis on the properties of this metabolism in tumor cells.